Abstract Since Ramon y Cajal, neuroscientists have speculated that even the most complex brain functions might eventuallybeunderstoodatthelevelofneuronalcelltypesandtheirconnections.Unfortunately,ourunder? standingofthebrain'sextensivediversityofcelltypesandelaboratecircuitryremainsfarfromcomplete.For example,despitethehippocampusbeingessentialforlearningandmemoryanditsdysfunctionunderlyinga widevarietyofdevastatingneuropsychiatricdisorders,westilllackfundamentalknowledgeaboutitsconstit? uentcelltypesandtheirmolecularprofilesandconnectivity,slowingprogresstowardsamechanisticcircuit? levelunderstandingofmemoryformation.WeproposetoidentifyalloftheinterneuroncelltypesinareaCA1 ofthehippocampusanddeciphertheircanonicalconnectivity.Wehaveassembledastronginterdisciplinary team capable of combining cutting?edge technologies including high?throughput multi?cell patch recordings, morphologicalreconstructions,single?cellRNAsequencing,andmachinelearningtoachievetwomaingoals: 1)dissectCA1microcircuitorganizationbygeneratingamorphologicalandelectrophysiologicaltaxonomyof allinterneuroncelltypesinmouseCA1andmaptheirconnections;and2)derivetranscriptomicsignaturesof morphologicallydefinedCA1interneuronsusingournewlydevelopedPatch?seqmethod.Ourteamrecently implemented this interdisciplinary experimental strategy to successfully identify cell types in the neocortex anddissecttheirmicrocircuitry.Usingmulti?cellpatchclamprecording,wewillcharacterizetheelectrophysi? ologicalproperties,morphology,laminarlocationandconnectivityofthousandsofneuronsfrommouseCA1 hippocampus.Wewillalsoutilizeanew,highlysensitive,costeffectivetechniqueforsingle?cellRNAsequenc? ing(Smart?seq2)tomaptheirtranscriptomesandmachinelearningtechniquestoclassifycellsintomolecular types. Importantly, our high?throughput method will allow us to obtain morphological, electrophysiological and complete transcriptome information for single neurons, which cannot be achieved using other methods suchasdissociatingtissueforsingle?cellsequencing.In?housecustomizationandautomationhasreducedour sequencingcosts,enablingustosequencethousandsofcellswithinareasonablebudget.Celltypeidentifica? tionwillbevalidatedusingmorphological,electrophysiological,andmoleculartests.Identifyingallofthein? terneuron cell types that comprise CA1 and determining how they connect to each other will have a broad, paradigm?shiftingimpact.Forinstance,itwillcontributetoacircuit?levelunderstandingofthecomputations thattakeplaceinCA1,suchasmemoryformation.Fromaclinicalperspective,single?celltranscriptomedata willyieldapowerfulatlastoinvestigaterelationshipsbetweencelltypesandgenesrelatedtoneuropsychiatric diseasesandfacilitatecell?typeengineering.